Temperature volatility as a novel environmental trigger for immune thrombocytopenia: A retrospective case-control study Free

Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder marked by immune-mediated platelet destruction. Although viral triggers are well-recognized, non-infectious environmental contributors remain poorly defined. Temperature instability has been implicated in immune dysregulation across other inflammatory and cardiovascular conditions. We investigated whether fluctuations in environmental temperature—specifically short-term volatility—could act as a novel environmental trigger for ITP onset.

Methods: We conducted a retrospective case-control study of ITP and non-ITP thrombocytopenia admissions between January 2023 and August 2025 at Canberra Health Services, a tertiary-level, state-based healthcare system in Australia. Each patient's postcode and admission date were linked to daily meteorological data from the Meteostat API. Temperature volatility was defined as the cumulative absolute change in daily mean temperature over the 7 days preceding admission. A threshold of ≥10 °C (50 °F) was set for high volatility, based on biologically plausible thresholds in prior environmental health literature.

We tested associations using Fisher's exact test, logistic regression, 1,000 permutation simulations, and bootstrap confidence intervals. Additional analyses explored lag periods from 1 to 21 days, thresholds from 3 °C to 12 °C (37 °F to 54 °F), and reversal sequences. We also evaluated seasonal effects, subtype stratification, and matched-random controls.

Results: A total of 40 ITP cases and 15 controls were included (median age 43 years [range 1–95]; ITP median 33.5 years, controls median 67.0 years; 56.4% female; 28 unique postcodes). Among ITP cases, 23 (57.5%) were new-onset and 17 (42.5 %) were relapses. Presentations occurred year-round, with the highest peak in June and smaller peaks in January, February, March, August, and December. Median platelet count at presentation was 5 × 10⁹/L (mean 7 × 10⁹/L) in ITP patients, compared with 15 × 10⁹/L (mean 30 × 10⁹/L) in non-ITP controls. There were no significant gender differences between groups; however, cases were significantly younger than controls (p = 0.033).

High temperature volatility (≥10 °C in the 7 days prior to admission) was significantly associated with ITP onset on crude analysis (OR 4.35, p = 0.022) and remained significant after age adjustment (OR 3.54, p = 0.05). The association was confirmed by logistic regression (p = 0.022), bootstrap resampling (95% CI 1.25–19.69), and random-date permutation testing (2.6% of randomized models reached p < 0.05). The effect was temporally specific, disappearing when the exposure window was shifted to 14–21 days prior (OR 1.4, p = 0.74) or when random admission dates were simulated. No signal was detected in matched controls or in season-adjusted models. Lower volatility thresholds and wider lag windows diluted the effect.

Subgroup analysis showed high-volatility exposure in 68.2% of new-onset cases and 82.4% of relapsed ITP cases. Daily temperature spikes or drops, extreme temperatures (maximum ≥35 °C, minimum ≤5 °C), and humidity extremes were not associated with ITP onset.

Conclusions: This is the first study to demonstrate a statistically significant crude association between ambient temperature volatility and the onset of ITP, with a large effect size that persisted after age adjustment. The specificity of the effect to the 1–7 day pre-admission window, the strength of association, and its reproducibility across multiple statistical methods support the presence of a genuine biological signal.

Key limitations include the assumption that patients remained within their recorded residential postcode during the exposure window and the exclusion of non-hospitalized cases. Despite focusing on the most severe presentations of ITP, temperature volatility emerged as a consistent and temporally specific environmental correlate.

These findings introduce ambient temperature volatility as a novel, non-infectious immune stressor capable of acutely priming autoimmunity, and warrant validation in larger, multicenter cohorts alongside mechanistic investigations into how short-term climatic fluctuations may alter immune thresholds and trigger autoimmune disease onset.